Pharmacotherapy for panic disorder with or without agoraphobia in adults
- Peter P Roy-Byrne, MD
Peter P Roy-Byrne, MD
- Editor-in-Chief — Psychiatry
- Section Editor — Depressive Disorders
- Professor of Psychiatry and Behavioral Sciences
- University of Washington School of Medicine
Panic disorder is a chronic illness characterized by recurrent panic attacks, at least some of which are unexpected, accompanied either by anxiety about having future attacks or about the implications of attacks (eg, undiscovered medical illness, possible sudden death or insanity), or by a change in behavior due to attacks (eg, avoidance of certain situations, recurrent requests for medical tests) .
While up to a third of the population will have a panic attack in their lifetime, only about 10 percent of this group (about 3 percent of the population) will go on to develop panic disorder . Clinical trials have found that both pharmacologic and psychotherapeutic approaches are efficacious for panic disorder. With the revision of DSM-IV to DSM-5, agoraphobia is diagnosed independently of panic disorder . Agoraphobia frequently but not always accompanies panic disorder.
Pharmacotherapy for panic disorder is discussed here. The epidemiology, pathogenesis, clinical manifestations, course, and diagnosis of panic disorder are discussed separately. Psychotherapy for panic disorder and for agoraphobia are also reviewed separately. (See "Panic disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Psychotherapy for panic disorder with or without agoraphobia in adults".)
APPROACH TO TREATMENT
Our approach to selecting among treatments for panic disorder, including the use of pharmacotherapy and psychotherapy, is discussed separately. (See "Approach to treating panic disorder with or without agoraphobia in adults".)
Several classes of medication have shown efficacy for symptoms of panic disorder (attack frequency, anticipatory anxiety, and phobic avoidance): selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCADs), monoamine oxidase inhibitors (MAOIs), and benzodiazepines. These drugs differ in the extent of supporting evidence, side effect profile, and in the case of benzodiazepines, their potential for abuse [3-6].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
- Norton CR, Cox BJ, Malan J. Nonclinical panickers: A critical review. Clin Psychol Rev 1992; 12:121.
- Bakker A, van Balkom AJ, Spinhoven P. SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis. Acta Psychiatr Scand 2002; 106:163.
- Otto MW, Tuby KS, Gould RA, et al. An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. Am J Psychiatry 2001; 158:1989.
- Mitte K. A meta-analysis of the efficacy of psycho- and pharmacotherapy in panic disorder with and without agoraphobia. J Affect Disord 2005; 88:27.
- Wilkinson G, Balestrieri M, Ruggeri M, Bellantuono C. Meta-analysis of double-blind placebo-controlled trials of antidepressants and benzodiazepines for patients with panic disorders. Psychol Med 1991; 21:991.
- Slaap BR, den Boer JA. The prediction of nonresponse to pharmacotherapy in panic disorder: a review. Depress Anxiety 2001; 14:112.
- Roy-Byrne PP, Russo J, Cowley DS, Katon WJ. Unemployment and emergency room visits predict poor treatment outcome in primary care panic disorder. J Clin Psychiatry 2003; 64:383.
- Michelson D, Allgulander C, Dantendorfer K, et al. Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial. Br J Psychiatry 2001; 179:514.
- Oehrberg S, Christiansen PE, Behnke K, et al. Paroxetine in the treatment of panic disorder. A randomised, double-blind, placebo-controlled study. Br J Psychiatry 1995; 167:374.
- Pohl RB, Wolkow RM, Clary CM. Sertraline in the treatment of panic disorder: a double-blind multicenter trial. Am J Psychiatry 1998; 155:1189.
- Rapaport MH, Wolkow R, Rubin A, et al. Sertraline treatment of panic disorder: results of a long-term study. Acta Psychiatr Scand 2001; 104:289.
- Lepola UM, Wade AG, Leinonen EV, et al. A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder. J Clin Psychiatry 1998; 59:528.
- Deltito JA, Argyle N, Buller R, et al. The sequence of improvement of the symptoms encountered in patients with panic disorder. Compr Psychiatry 1991; 32:120.
- Stein M, Goin M, Pollack M, et al. Practice Guideline for the treatment of patients with panic disorder: Second edition. Am J Psychiatry 2009; 166 (2):1.
- Cowley DS, Ha EH, Roy-Byrne PP. Determinants of pharmacologic treatment failure in panic disorder. J Clin Psychiatry 1997; 58:555.
- Simon NM, Otto MW, Worthington JJ, et al. Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial. J Clin Psychiatry 2009; 70:1563.
- Pollack MH, Lepola U, Koponen H, et al. A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. Depress Anxiety 2007; 24:1.
- Bradwejn J, Ahokas A, Stein DJ, et al. Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study. Br J Psychiatry 2005; 187:352.
- Montgomery SA, Baldwin DS, Blier P, et al. Which antidepressants have demonstrated superior efficacy? A review of the evidence. Int Clin Psychopharmacol 2007; 22:323.
- Johnson EM, Whyte E, Mulsant BH, et al. Cardiovascular changes associated with venlafaxine in the treatment of late-life depression. Am J Geriatr Psychiatry 2006; 14:796.
- Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J Clin Psychiatry 2006; 67 Suppl 4:14.
- Cheeta S, Schifano F, Oyefeso A, et al. Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998-2000. Br J Psychiatry 2004; 184:41.
- Rubino A, Roskell N, Tennis P, et al. Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study. BMJ 2007; 334:242.
- Kimmel R, Roy-Byrne PP, Cowley DS. Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia and social anxiety disorder. In: A Guide to Treatments That Work, 4th ed, Nathan PE, Gorman JM (Eds), Oxford University Press, New York 2015. p.337.
- Zitrin CM, Klein DF, Woerner MG, Ross DC. Treatment of phobias. I. Comparison of imipramine hydrochloride and placebo. Arch Gen Psychiatry 1983; 40:125.
- Sheehan DV, Ballenger J, Jacobsen G. Treatment of endogenous anxiety with phobic, hysterical, and hypochondriacal symptoms. Arch Gen Psychiatry 1980; 37:51.
- Montañés-Rada F, De Lucas-Taracena MT, Sánchez-Romero S. Mirtazapine versus paroxetine in panic disorder: an open study. Int J Psychiatry Clin Pract 2005; 9:87.
- Sarchiapone M, Amore M, De Risio S, et al. Mirtazapine in the treatment of panic disorder: an open-label trial. Int Clin Psychopharmacol 2003; 18:35.
- Milan Pavlovic Z. Remission of panic disorder with mirtazapine augmentation of paroxetine: a case report. Prim Care Companion J Clin Psychiatry 2007; 9:396.
- Spiegel DR, Kolb R. Treatment of irritable bowel syndrome with comorbid anxiety symptoms with mirtazapine. Clin Neuropharmacol 2011; 34:36.
- Schweizer E, Patterson W, Rickels K, Rosenthal M. Double-blind, placebo-controlled study of a once-a-day, sustained-release preparation of alprazolam for the treatment of panic disorder. Am J Psychiatry 1993; 150:1210.
- Herman JB, Brotman AW, Rosenbaum JF. Rebound anxiety in panic disorder patients treated with shorter-acting benzodiazepines. J Clin Psychiatry 1987; 48 Suppl:22.
- Herman JB, Rosenbaum JF, Brotman AW. The alprazolam to clonazepam switch for the treatment of panic disorder. J Clin Psychopharmacol 1987; 7:175.
- Roy-Byrne PP, Cowley D. Pharmcologic treatments for panic disorder, generalized anxiety disorders, specific phobia and social anxiety disorders. In: A guide to treatments that work, 3rd ed, Nathan P, Gorman J (Eds), Oxford University Press, New York 2007. p.337.
- Goddard AW, Brouette T, Almai A, et al. Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry 2001; 58:681.
- Lydiard RB, Lesser IM, Ballenger JC, et al. A fixed-dose study of alprazolam 2 mg, alprazolam 6 mg, and placebo in panic disorder. J Clin Psychopharmacol 1992; 12:96.
- Ciraulo DA, Sands BF, Shader RI. Critical review of liability for benzodiazepine abuse among alcoholics. Am J Psychiatry 1988; 145:1501.
- Verdoux H, Lagnaoui R, Begaud B. Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies. Psychol Med 2005; 35:307.
- Uhde TW, Stein MB, Post RM. Lack of efficacy of carbamazepine in the treatment of panic disorder. Am J Psychiatry 1988; 145:1104.
- Zwanzger P, Eser D, Nothdurfter C, et al. Effects of the GABA-reuptake inhibitor tiagabine on panic and anxiety in patients with panic disorder. Pharmacopsychiatry 2009; 42:266.
- Pande AC, Pollack MH, Crockatt J, et al. Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol 2000; 20:467.
- Hirschmann S, Dannon PN, Iancu I, et al. Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial. J Clin Psychopharmacol 2000; 20:556.
- Uhde TW, Stein MB, Vittone BJ, et al. Behavioral and physiologic effects of short-term and long-term administration of clonidine in panic disorder. Arch Gen Psychiatry 1989; 46:170.
- Goddard AW, Mahmud W, Medlock C, et al. A controlled trial of quetiapine XR coadministration treatment of SSRI-resistant panic disorder. Ann Gen Psychiatry 2015; 14:26.
- Lepola U, Bergtholdt B, St Lambert J, et al. Controlled-release paroxetine in the treatment of patients with social anxiety disorder. J Clin Psychiatry 2004; 65:222.
- Donovan MR, Glue P, Kolluri S, Emir B. Comparative efficacy of antidepressants in preventing relapse in anxiety disorders - a meta-analysis. J Affect Disord 2010; 123:9.
- Ferguson JM, Khan A, Mangano R, et al. Relapse prevention of panic disorder in adult outpatient responders to treatment with venlafaxine extended release. J Clin Psychiatry 2007; 68:58.
- Mavissakalian MR, Perel JM. Long-term maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia. Arch Gen Psychiatry 1999; 56:821.
- Noyes R Jr, Garvey MJ, Cook B, Suelzer M. Controlled discontinuation of benzodiazepine treatment for patients with panic disorder. Am J Psychiatry 1991; 148:517.
- APPROACH TO TREATMENT
- - Selective serotonin reuptake inhibitors
- Side effects
- - Serotonin-norepinephrine reuptake inhibitors
- Side effects
- - Tricyclic antidepressants
- Side effects
- - Monoamine oxidase inhibitors
- - Mirtazapine
- - Efficacy
- - Dosing
- - Side effects
- Risk of addiction
- Other medications
- DURATION OF TREATMENT
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS